Rotenon ile İndüklenen İn Vitro Parkinson Hastalığı Modelinde Glukagon Benzeri Peptid-1 Analoğu Ekzenatidin Nöron Sağkalımına Etkisi

Yıl 2019, Cilt: 10 Sayı: 4, 362 - 368, 13.12.2019

Mümin Alper Erdoğan , Dilek Taşkıran

Öz

Parkinson hastalığı (PH), beyinde substansiya
nigrada bulunan dopaminerjik nöronların hasarı ve buna eşlik eden striatumda
dopamin eksikliği sonucunda gelişen, bradikinezi, rijidite ve postural
instabilite ile seyreden kronik ve ilerleyici bir nörodejeneratif hastalıktır.
Çalışmalar genetik ve yaşlanma, pestisid ve ağır metallere maruziyet gibi
çevresel faktörlerin hastalığın etiyopatogenezinde önemli role sahip
olabileceğine işaret etmektedir. Rotenon, deneysel PH modeli oluşturmak ve hastalığın
mekanizmasını araştırmak amacıyla kullanılan organik bir pestisidtir. Bu
çalışmada amacımız insan nöroblatoma hücre serisi olan SH-SY5Y hücrelerinde
rotenonun toksik etkisini ve aynı zamanda GLP-1 analoğu olan ekzenatidin
rotenon nörotoksisitesine karşı koruyucu etkili olup olmadığını araştırmaktır.
Bu amaçla SH-SY5Y hücre kültürleri çeşitli dozlardaki rotenon ile 24 saat
boyunca inkübe edildi. Ekzenatidin koruyucu etkisi yine farklı dozlardaki
ekzenatidin rotenon ile birlikte kültür medyumuna eklenmesi ve 24 saat inkübe
edilmesi ile incelendi. Rotenon ve ekzenatidin etkileri hücre canlılığı,
klonojenik aktivite, morfolojik inceleme ve apopitotik hücre ölümünün
değerlendirilmesi ile belirlendi. Sonuçlarımız rotenon eklenen gruplarda doza
bağlı olarak ve anlamlı düzeyde hücre canlılığının ve klonojenik aktivitenin
azaldığını gösterdi. Ayrıca rotenon eklenen hücrelerde belirgin olarak
morfolojik değişim olduğu ve apopitotik hücre ölümünde artış olduğu gözlendi.
Ortama ekzenatidin eklenmesi ise hücre canlılığının ve klonojenik aktivitenin
korunmasına, apopitotik hücre ölümünde azalmaya neden oldu. Sonuç olarak;
bulgularımız rotenonun SH-SY5Y hücrelerinde nörotoksik etkilerinin olduğunu ve in vitro PH modeli oluşturmak amacıyla
kullanılabileceğini gösterdi. Ayrıca, sonuçlarımız ekzenatidin nöronal
hücrelerde rotenon ile indüklenen toksisiteye karşı nöroprotektif etkiye sahip
olabileceğini gösterdi.

Anahtar Kelimeler

Parkinson, Rotenon, Ekzenatid, Nörotoksisite, Nöroprotektif

Destekleyen Kurum

Ege Üniversitesi Bilimsel Araştırma Projeleri

Proje Numarası

16-TIP-056

Teşekkür

Bu çalışma Ege Üniversitesi Bilimsel Araştırma Projeleri’nin 16-TIP-056 no’lu projesi kapsamında desteklenmiştir.

Effect of Glucagon like Peptide-1 Analogue Exenatide on Neuron Survival in Rotenone-Induced In Vitro Parkinson's Disease Model

Öz

Parkinson's disease (PD) is one the most common
neurodegenerative disorder characterized by bradykinesia, tremor, rigidity and
postural instability as a result of progressive degeneration of the
dopaminergic neurons in substantia nigra pars compacta (SNc) and dopamine
decrease in the striatum. Accumulating data recommends that combination of
genetic and environmental factors including aging, exposure to pesticides, and
heavy metals may have significant roles in the pathogenesis of PD. Rotenone, an
organic pesticide, is commonly used for investigating the mechanism of neuronal
degeneration in experimental PD models. In the present study, we aimed to
investigate the effects of rotenone on SH-SY5Y human neuroblastoma cells, and
also the neuroprotective effects of exenatide, a GLP-1 analogue, against
rotenone-induced neurotoxicity. Briefly, to induce rotenone-induced
neurotoxicity, SH-SY5Y cells were exposed to various doses of rotenone for 24
hours. To explore the neuroprotective effects of exenatide, different doses of
exenatide were added into the medium with or without rotenone for 24 hours.
Cell viability, clonegenic potential, morphological alterations, and apoptotic
cell death were evaluated. Our results demonstrated a dose-dependent and
significant decrease in cell viability in rotenone-exposed groups. Also,
rotenone-treated group showed significant morphological alterations, decreased
clonogenic potential and increased apoptosis. However, treatment of the cells
with exenatide significantly improved cell viability and clonogenic activity,
and reduced apoptotic cell death. In conclusion, these findings suggested that
rotenone can induce neurotoxicity in neuronal cells and can be used to
establish in vitro PD model. In
addition, exenatide may have neuroprotective effects on neuronal cells against
rotenone-induced neurotoxicity.

Anahtar Kelimeler

Parkinson, Rotenone, Exenatide, Neurotoxicity, Neuroprotective

Proje Numarası

16-TIP-056

Kaynakça

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